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Table 5.1 Recurrent brief depression (RBD), recurrent brief hypomania (RBM), and recurrent
brief anxiety (RBA): association with mood disorders

BP-II Minor BP Hypomania MDD
(n ¼ 89) (n ¼ 59) (n ¼ 23) (n ¼ 101)
(%) (%) (%) (%)
Diagnoses

RBD (rbdr7999) 43.8 71.2 38.6
RBM (rbm8199) 20.2 17.0 17.4
RBD þ RBM (rbmd7999) 55.1 72.9 17.4
RBA 43.8 32.2 8.7 35.3

BP, bipolar; MDD, major depressive disorder.




RBD RBD

89 13.7

6 69 1.4 5.0
12 0.9
2.0 4.9
0.6
11 4 45
RBM RBA
RBM RBA




Association OR (95% CI)
RBD — RBM 2.9 (1.4 “ 5.9)
RBD — RBA 5.2 (3.4 “ 8.0)
RBM — RBA 3.8 (1.7 “ 8.2)

Fig. 5.3 Longitudinal associations between recurrent brief psychiatric syndromes. Left side: number
of cases; right side: weighted prevalence rates. Odds ratios are adjusted for sex and stratified
sampling. RBD, recurrent brief depression; RBM, recurrent brief mania/hypomania; RBA,
recurrent brief anxiety; OR, odds ratio; CI, 95% confidence interval.



The value of RBD, RBM, and hypomanic symptoms as a predictor
of BP-II disorder
Of 132 first observed cases of RBD, 32% developed manic symptoms prospectively
and a further 15% developed BP-II/MinBP disorders (the categories are not
mutually exclusive).
117 Recurrent brief depression


There was considerable stability of RBD over the years; 31% of RBD cases
received a diagnosis of RBD again in a later interview.
Three of 23 cases of RBM (11.5%) were followed by BP-II disorder, and 8% of
the 38 cases with BP-II disorder were preceded by RBM.
Of the subjects with hypomanic symptoms, seven of 122 cases (5.7%) developed
BP-II disorders prospectively; in a follow-up, seven of 38 BP-II cases (18%) were
found to have manifested hypomanic symptoms in earlier interviews.


Combined versus pure mood disorders (Table 5.2)
Gender
A marked female preponderance (88%) was only found in combined major
depression (MDD þ RBD). In most other groups with sufficiently large numbers,
the female preponderance was marginal (53“60%).

Diagnostic overlap
RBM overlapped with pure BP-II disorder, combined BP-II, and combined
MinBP in about 20% of cases; if symptoms (RBMS) were included, that overlap
rose to about 35%.
The group of pure MinBP (without RBD) is small and not conclusive. The high
rates of RBA (40“59%) among all subgroups of mood disorders associated with
RBD are remarkable; this is compatible with the high odds ratio (OR) of 5.2 shown
in Figure 5.3.

Family history
From a genetic point of view, the results are very interesting: they demonstrate
that, compared to pure BP-II and pure MinBP, the combined-disorder groups
tended to have higher rates of positive family histories for mania, depression, and
anxiety. It is important that, compared to the control group, none of the pure
depressed groups had an elevated rate of a family history of mania.

Clinical characteristics
A number of variables reflect the severity of the illness. Most demonstrate the
greater severity of illness in the combined groups: higher rates of subjective or
social consequences of their hypomanic symptoms (therefore meeting more
often the strict criteria for hypomania), higher rates of treatment and medication
for depression, and higher distress scores due to depression. On the other hand,
none of the subjects reported being distressed in any way by hypomanic
symptoms.
Table 5.2 Bipolar II (BP-II), minimum bipolar (MinBP), and major depressive disorder (MDD) subclassified by presence of recurrent brief depression
(RBD)

1 2 3 4 5 6 7 8 1“7
BP-II RBD BP-II MDD RBD MDD MinBP RBD MinBP RBD pure Controls
(n ¼ 39) (n ¼ 50) (n ¼ 39) (n ¼ 62) (n ¼ 42) (n ¼ 17) (n ¼ 60) (n ¼ 138)
P
(%) (%) (%) (%) (%) (%) (%) (%)
Prevalence rates (age 20“41 years) 4.3 6.7 3.5 7.9 6.0 3.4 7.5 42.4
Females 59.6 57.7 87.9 57.9 54.0 67.9 53.2 42.5 0.4804
RBM
RBM threshold (RBM) 20.5 20.0 21.4 5.9 NC
35.9 34.0 33.3 17.7 NC
RBMS subthreshold þ RBM
Cyclothymia (>49% days/1 year) 14.3 23.5 NC
Recurrent brief anxiety 59.0 32.0 43.6 17.7 40.5 11.8 43.3 4.9 0.0003
Family history (FH)
71.8 50.0 74.4 57.9 68.3 64.7 55.8 30.0 0.0373
FH þ depression
20.5 10.4 2.9 4.0 10.0 11.8 4.4 4.2 0.0001
FH þ mania
48.7 34.0 48.7 19.3 43.9 23.5 34.6 15.4 0.0001
FH þ anxiety
Clinical consequences
Suicide attempts 38.5 16.0 25.6 22.6 7.1 4.9 11.7 2.7 0.0001
Subjective or social consequences of hypomania 53.9 48.0 40.5 29.4 NC
Consequences of hypomania or depression 64.1 55.1 61.1 42.9 47.6 47.1 36.0
Lifetime treatment of depression 82.5 60.0 69.2 50.0 66.7 52.9 46.7 0.0078
Work impairment 100 82.0 100 89.9 100 82.4 100 NC
Maximum distress depression (mean) 86.9 80.6 85.1 83.3 81.3 81.7 77.4 0.1717
Onset and course
Age of onset (mean) (years) 12.0 13.3 12.3 15.3 12.6 14.4 16.1 0.0002
Age of first treatment (mean) (years) 21.7 22.8 22.0 23.4 23.2 22.3 22.6 0.0002
Course
Recurrent 100 95.2 81.8 90.9 100 90 100 NC
Chronic 4.8 18.2 9.1 10 NC
Rapid-cycling depression 69.2 54.0 61.5 48.4 90.5 76.5 98.3 0.0001
Rapid-cycling (mania depression) 82.2 82.0 61.5 48.4 100 88.2 98.3 0.0001
Seasonal depression (fall/winter) 64.1 55.1 61.1 42.9 47.6 47.1 36.0 0.1014
Spring depression 20.5 12.2 19.4 3.6 19.1 5.9 4.0 0.0278
Summer depression 7.7 2.0 5.6 0 2.4 0 4.0 NC
Atypical depression DSM-IV 69.2 30.6 52.8 39.3 45.2 35.3 32.0 6.0 0.0001
Atypical depression: Zurich criteria 82.1 44.9 58.3 42.9 45.2 41.2 34.0 6.0 0.0001
Personality ˜˜ups and downs™™ 41.0 36.0 20.5 19.4 35.7 23.5 13.3 3.8 0.0126
Depressive personality disorder 33.3 8.9 14.3 8.3 29.0 5.9 27.3 4.3 0.0047
Anxious personality 33.3 10.0 25.6 4.8 23.8 11.8 16.7 3.8 0.0038
Sociopathy (including adulthood) 12.8 8.0 5.1 11.3 4.8 3.3 1.6 NC
Conduct problems (adolescence) 28.2 47.9 17.1 25.5 24.4 29.4 23.4 20.2 0.0558
Thefts 7.7 18.8 17.1 16.0 7.5 23.5 2.2 10.5 NC
Truancy 18.0 18.8 8.6 14.0 5.0 8.7 2.1 NC
Runaway 10.3 8.3 5.7 8.0 11.8 1.05 NC
Frequent fights 5.1 20.8 5.7 6.0 10.0 8.7 5.3 NC
Offenses 33.3 24.0 18.0 25.8 11.9 23.5 15.0 6.0 0.2194
Freiburg Personality Inventory at age 35 years
Aggressiveness 20.6 18.3 17.8 12.6 19.5 20.4 18.8 14.6 0.6914
Extroversion 16.9 19.9 13.9 19.4 17.5 18.0 16.9 18.5 0.0161
Neuroticism 20.4 17.5 20.0 16.9 20.5 17.7 18.7 13.1 0.0889
Impulsivity/irritability 25.3 21.3 23.0 22.1 22.8 21.2 22.3 17.1 0.0001
Comorbidity
Anxiety disorders 71.8 58.0 69.2 45.2 50.0 23.5 51.7 13.0 0.0072
DSM-III panic disorder 15.4 18.0 20.5 4.8 16.7 5.9 11.7 1.6 0.2314
Table 5.2 (cont.)


1 2 3 4 5 6 7 8 1“7
BP-II RBD BP-II MDD RBD MDD MinBP RBD MinBP RBD pure Controls
(n ¼ 39) (n ¼ 50) (n ¼ 39) (n ¼ 62) (n ¼ 42) (n ¼ 17) (n ¼ 60) (n ¼ 138)
P
(%) (%) (%) (%) (%) (%) (%) (%)
Repeated panic attacks 38.5 34.0 51.3 16.1 31.0 5.9 36.7 6.5 0.1378
DSM-III general anxiety disorder 43.6 34.0 25.6 24.2 26.2 11.8 21.7 3.8 0.3615
Agoraphobia 15.4 16.0 18.0 8.1 11.9 11.8 8.3 3.8 NC
Social phobia 30.8 20.0 33.3 14.5 23.8 11.8 16.7 3.8 0.1715
Specific phobia 28.2 18.0 25.6 14.5 16.7 17.7 6.7 6.0 0.1121
Obsessive-compulsive disorder 23.8 11.4 22.2 17.4 6.5 2.7 NC
Obsessive-compulsive syndrome 23.1 14.0 28.2 8.1 11.9 29.4 11.7 9.2 0.0507
Bulimia 2.6 4.1 2.8 5.4 7.1 2.0 NC
Binge-eating 23.1 22.5 16.7 14.3 16.7 11.8 10.0 3.4 0.6136
Substance abuse/dependence 61.5 50.0 23.1 32.3 26.2 47.1 18.3 15.1 0.0001
Alcohol abuse/dependence 56.1 36.0 7.7 25.8 23.8 35.3 11.7 11.9 0.0001
Cannabis abuse/dependence 18.0 20.0 12.8 14.5 7.1 23.5 3.3 6.5 0.0861
Benzodiazepine abuse 10.3 8.0 7.7 11.3 4..8 5.9 5.0 1.0 0.8489
Opiate abuse/dependence 10.3 4.0 5.1 4.8 2.4 11.8 1.1 NC
Psychostimulant abuse/dependence 12.8 10.0 2.6 6.5 2.4 5.9 1.7 3.8 NC
Tobacco dependence 64.1 55.1 47.2 46.3 52.4 64.7 38.0 33.3 0.2121

NC, not computed, small cell occupancy; RBM, recurrent brief mania; RBMS, RBM symptoms; DSM-IV, Diagnostic and Statistical Manual of Mental
Disorders
121 Recurrent brief depression



Table 5.3 Mood disorder with recurrent brief depression (RBD) versus mood disorders
without RBD: associations with clinical characteristics

Dependent variable OR P CI 95%

Family history of depression 1.99 0.01 1.17 3.39
Family history of mania 1.52 0.36 0.62 3.70
Family history of anxiety 2.56 0.00 1.49 4.38
Suicide attempts 1.29 0.43 0.69 2.40
Lifetime treatment depression 2.12 0.01 1.22 3.68
Seasonal depression 1.37 0.24 0.81 2.30

OR, odds ratio; CI, confidence interval.


Onset and course
In all groups the age of onset of first symptoms was early, occurring in 90% of cases
before the age of 21. A chronic course was mainly observed in major depression but
not in bipolar spectrum disorders, whose course patterns tended to be characterized
by recurrent episodes and very high rapid-cycling rates (80% or more).
Overall, bipolarity was associated with seasonal depression. Seasonal depression
in fall and winter was markedly present in all the mood-disorder subgroups,
especially in combined BP-II and combined MDD. Rapid-cycling depression was
also strongly associated with these two subgroups (69% and 62% respectively);
rapid-cycling depression was found in about half of the pure BP-II and MDD cases.


Associations with other psychiatric disorders
Overall, the combined groups showed significantly elevated comorbidity with all
subgroups of anxiety disorders, with the exception of agoraphobia. However, we
found no systematic relationship between substance abuse/dependence and RBD;
but significant differences were found between bipolar and depressive spectrum
disorders. Table 5.3 shows the results of a logistic regression that tested associa-
tions between all three combined groups (BP-II, Min-BP, MDD with RBD) versus
the pure groups (without RBD) of mood disorders (as dependent variable), with
some of the characteristics listed in Table 5.2 as independent variables. RBD was
significantly associated with a family history of depression (OR ¼ 2.0) and anxiety
(2.6) and double the lifetime treatment rate for depression (OR 2.1).

Personality
Combined bipolar and depressive groups (with RBD) demonstrated significantly
more personality disorders and certain personality traits, such as mood lability
122 J. Angst et al.


(assessed as ˜˜frequent ups and downs™™), anxious personality, and depressive
personality disorder, whereas, surprisingly, the reverse trend was present for
conduct problems in childhood and adolescence (Table 5.2). The combined
groups also showed lower extroversion scores and higher neuroticism scores
than the pure diagnostic groups. It is noteworthy that in all three combined groups
the impulsivity/irritability scores were significantly higher. A comparison of mean
impulsivity scores revealed highly significant differences between the following
four groups (Kruskal“Wallis test: 68.5, df ¼ 3, P < 0.0001): (1) MDE þ RBD: 17.1
(8.1); (2) MDE: 14.7 (7.2); (3) RBD: 18.5 (7.4); and (4) all other subjects of the
sample: 11.0 (5.9). High impulsivity/irritability was the most characteristic per-
sonality feature of RBD subjects.


Suicide attempts
The significance of RBD is illustrated by the highest suicide attempt rates found in
combined BP-II (38.5%) and combined MDD (25.6%). Compared to controls,
subjects suffering from pure RBD had a fourfold higher suicide attempt rate
(11.7% versus 2.7%), but the suicide attempt rates in pure BP-II subjects was
slightly higher (16%) and higher still in pure MDD (22.6%) (Table 5.2). In a
logistic regression we found a significant association of suicide attempts (as the
dependent variable) with all three diagnoses, BP-II (OR 9.8; 95% confidence
interval 3.5“27.4); MDD (11.2; 4.1“30.5); and RBD (2.1; 1.3“3.5).
Disregarding the bipolar“unipolar distinction, we also compared the suicide
attempt rates of subjects with MDE, RBD, and its combination. As expected, the
combined group (MDE þ RBD) had the highest suicide attempt rate, with 32.9%; the
rate for the MDE group was 19.5%, for RBD 9.7%, and the rate for all other subjects
together (including anxiety disorders, and substance abuse/dependence) was 3.7%.
Considering the hypothesis that a factor underlying impulsive/aggressive beha-
vior (Angst and Clayton, 1998; Mann et al., 1999) might lower the threshold for
acting on suicidal ideas, we carried out logistic regression analyses of suicide
attempts as the dependent variable. Female gender (OR ¼ 1.9; 1.1“3.3), MDD
(OR ¼ 4.5; 2.6“7.9), and RBD (OR ¼ 1.9; 1.1“3.2) were significantly associated
with suicide attempts, but this was not the case for impulsivity, aggressiveness, as
self-rated personality traits, or a positive family history of suicides.


Discussion
The main findings of this study shed further light on the clinical significance of the
combination of major mood disorders, BP-II and MDD with RBD versus pure
major mood disorders without RBD.
123 Recurrent brief depression

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